Division of Gastroenterology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Annu Rev Physiol. 2013;75:263-88. doi: 10.1146/annurev-physiol-030212-183741. Epub 2012 Nov 26.
The small and large intestines are tubular organs composed of several tissue types. The columnar epithelium that lines the inner surface of the intestines distinguishes the digestive physiology of each region of the intestine and consists of several distinct cell types that are rapidly and continually renewed by intestinal stem cells that reside near the base of the crypts of Lieberkühn. Notch signaling controls the fate of intestinal stem cells by regulating the expression of Hes genes and by repressing Atoh1. Alternate models of Notch pathway control of cell fate determination are presented. Roles for Notch signaling in development of the intestine, including mesenchymal and neural cells, are discussed. The oncogenic activities of Notch in colorectal cancer, as well as the tumor suppressive activities of Atoh1, are reviewed. Therapeutic targeting of the Notch pathway in colorectal cancers is discussed, along with potential caveats.
小肠和大肠是管状器官，由几种组织类型组成。排列在肠内表面的柱状上皮区分了肠的每个区域的消化生理学，并且由位于 Lieberkühn 隐窝底部附近的肠干细胞迅速和连续地更新，Notch 信号通过调节 Hes 基因的表达和抑制 Atoh1 来控制肠干细胞的命运。提出了 Notch 途径控制细胞命运决定的替代模型。讨论了 Notch 信号在包括间充质和神经细胞在内的肠发育中的作用。还回顾了 Notch 在结直肠癌中的致癌活性以及 Atoh1 的肿瘤抑制活性。讨论了 Notch 途径在结直肠癌中的治疗靶向，以及潜在的注意事项。
